Chemistry Reference
In-Depth Information
To measure and document robustness, the following HPLC parameters should be
routinely monitored:
• Critical peak pair resolution
R
s
• Column plate number
N
(or peak width in gradient elution)
• Retention time
t
R
• Tailing factor
TF
• Peak area (and/or height) and concentration
Replicate injections will improve the estimates (e.g., %RSD) of the effect of a
parameter change. In many cases, multiple peaks are monitored, particularly when
some combination of acidic, neutral, or basic compounds are present in the sample.
Often, the results of robustness studies are included in the method development
report; such examples, plus corrective instructions, will help to translate robustness
studies into practical method implementation. Robustness is discussed in Chapter 5
in greater detail.
4.4 vAlIdAtIon AccordIng to metHod type
Guidelines recognize that it is not always necessary to evaluate every analytical per-
formance parameter for every type of method. The type of method and its intended
use dictate which performance characteristics need to be investigated, as summa-
rized in Table 4.7 [2,4]. Both the USP and ICH divide analytical methods into four
separate categories that generally apply to drug substances and drug products:
• Category 1: Assays for the quantiication of major components or active
ingredients
• Category 2: Determination of impurities or degradation products
• Category 3: Determination of performance characteristics
• Category 4: Identiication tests
Specific examples of the different types of methods in each category are discussed
in more detail in Chapter 7.
4.5 documentAtIon
Validation documentation includes the protocol used to carry out the validation, the
analytical test method, and the validation report. These documents should be written
as controlled documents as part of a quality system that ensures compliance with
appropriate regulations.
4.5.1 v
AlIdAtIon
P
rotocol
The validation protocol specifies the requirements (validation procedures and accep-
tance criteria) to be satisfied. Where possible, the protocol should reference standard
operating procedures (SOPs) for specific work instructions and analytical methods.
